1. Field of the Invention
The invention relates to a liquid-transport device comprising a liquid-tight support on which there is applied a start zone for applying transport liquid to be transported and a target zone into which the transport liquid is to be transported and also a conduction zone which extends between the start zone and the target zone and which comprises a microporous transport layer in which the transport liquid flows by capillary force from the start zone to the target zone.
2. Description of the Related Art
The invention further relates to an analytical test device using such a liquid-transport device.
Such liquid-transport devices and analytical test devices are known from US 2006/0205059 A1.
It discloses—in a specific embodiment—an analytical test device known in general as a lateral flow immunoassay.
The lateral flow test is based on capillary force-driven liquid transport in a thin layer of microporous, open-pored material. Microporous material is understood here to mean in general a material having a mean pore size of approximately 0.1 to 50 micrometers and a volume fraction of the pores of at least 30%. Cellulose nitrate applied to a liquid-tight support, for example a glass or plastic support, in a thin layer is typically used for this purpose. A liquid to be tested, which is referred to here as sample liquid or, neutrally, as transport liquid, is applied to the microporous layer at a designated site of the test device. This can, for example, be achieved by pipetting of the transport liquid or by dipping of certain areas of the test device into the transport liquid or by other means. The start zone is frequently supplemented with a sponge-type or nonwoven-type liquid reservoir to increase the liquid uptake capacity thereof, and in the context of the present invention it is only important that the microporous transport layer is contacted with the transport liquid only at one or more defined sites, viz., the start zone(s), at a given start time. In the lateral flow test, the start zone is typically covered with a selective binder, which can be a specific antibody against an analyte presumably contained in the transport liquid, such that the specific binder, in the dry state, is fixed in the start zone and, in the moistened state, i.e., after application of the transport liquid, is movable and can flow with said liquid. The selective binder is usually labeled with a detectable label, for example a fluorescent label, a gold or latex particle, a radioactive label, or by other means. As a result of binding of the selective binder to analyte actually contained in the transport liquid, the latter is thus labeled. By means of the capillary force in the microporous transport layer, the transport liquid, and with it the labeled analyte or free, selective binder, flows along the extension direction of the transport layer toward a predetermined target zone. The design of the target zone, including the number of target zones, depends on the purpose and design of the respective test. A target zone is frequently defined by the application of selective binders for the analyte that are immobilized in said zone. In the present context, immobilized means that the selective binders of the target zone are stationary both in the dry state and in the moistened state. The analyte already labeled with the selective binder of the start zone is bound to the immobilized selective binder of the target zone and thus fixed in the target zone. This is said to be a so-called sandwich reaction. This leads to an accumulation of the detectable label in the target zone. Such an accumulation normally only occurs when analyte is actually present in the transport liquid. Otherwise, the labeled selective binders of the start zone which are not bound to an analyte flow through the target zone. In such a test design, accumulation of the label in the target zone thus means the presence of analyte in the transport liquid. However, other types of target zones are also known. In so-called control zones, which are frequently downstream of the aforementioned first type of target zones, nonspecific binders for the selective binder of the start zone can be immobilized, and so in this second control zone there is an accumulation of label in any case of a successful test procedure. It is also possible to design target zones, depending on the setup of the test, such that the coloring thereof is precisely indicative of non-presence of analyte in the transport liquid.
In such lateral flow tests or, more generally, in such liquid-transport devices, as form the basis of customary lateral flow tests, there is a significant optimization dilemma. Firstly, very rapid liquid transport from the start zone to the target zone is desired. This is very important especially for tests in the home-care sector, in which the test is carried out by lay people. An example is the known pregnancy strip test. A transport layer having a very large pore size would be favorable with regard to maximum transport rate. The greater the pore size, the lower the flow resistance and the greater the resulting wetting rate, i.e., the transport rate of the transport liquid in the conduction zone. Therefore, in customary lateral flow tests, cellulose nitrate layers having a pore size of distinctly more than 3 micrometers are frequently used as transport layers. Secondly, a very small pore size is favorable with regard to optimization of the signal sharpness in the target zone. The smaller the pore size, the greater the inner surface area of the microporous layer, and the greater the inner surface area, the more selective binders which are immobilizable in the target zone, i.e., the more catchers for labeled analytes which are available in the target zone, leading to an all the more sharper signal. Lastly, a third parameter also has to be taken into consideration in the case of this optimization dilemma, viz., the thickness of the transport layer. A very large layer thickness would be desirable with regard to the optimization of the transport rate. However, a large layer thickness also means a large volume of the transport layer, which volume has to be filled by the transport liquid in order to realize a liquid flow. However, for many analytical tests, there is only a small amount of liquid available, and so it is necessary to keep losses to a minimum. Under this aspect, a low layer thickness would therefore be desirable.
The known liquid-transport devices and the analytical test devices based thereon do not really solve the described optimization dilemma. On the contrary, compromises suboptimal in all aspects are realized which, depending on the specific purpose of the application, more or less ignore one or the other of the above-described aspects.
WO 03/025573 A1 discloses a further lateral flow test having multiple start and target zones, wherein especially the latter can also be comprehended as an extensive target zone having a plurality of partial zones. Incidentally, the device of said document likewise contains the above-described disadvantages.
WO 2007/149043 A1 discloses an analytical test device which dispenses with microporous material as transport layer and as start zone and target zone. On the contrary, said device has a liquid-impermeable support having a multiplicity of macroscopic projections which are close to one another and which are likewise composed of liquid-impermeable material, which projections are so close to one another that a capillary force-driven flow of the transport liquid from the start zone into the target zone is produced. A disadvantage of this device is the low possibility of fixing a sufficient amount of catchers in the target zone and of labeled selective binders in the start zone owing to the small surface area available for adhesion. In addition, the open structure formed by the projections is extremely susceptible to evaporation, and this has to be considered disadvantageous with regard to using the transport liquid very sparingly.
DE 102 24 568 A1 discloses a miniaturized microtiter plate which consists of a liquid-impermeable support and of separate projections composed of microporous material that are applied thereto. The individual projections can be covered with different binders or chemicals. A liquid to be analyzed can be applied separately to the projections in a drop-by-drop manner and be reacted with the impregnation binder and the impregnation chemical. This realizes a so-called microarray, which allows the observation of a multiplicity of reactions in a very confined space that are running in a spatially separated manner and at the same time. The individual sponges are separated from one another by trenches which are intended to prevent liquid exchange between the individual projections.
DE 10 2005 014 691 A1 discloses a further microarray device in which so-called wells, i.e., pans, are cut into a layer composed of microporous material such that they are closely adjacent to one another. The pans are suitable for accommodating living cells, and the microporous wall material which, in each case, connects the pans of a group to one another is used to uniformly distribute nutrient liquid onto the pans. The transport of the nutrient liquid within a group of pans follows driven by the capillary force established by the micropores of the wall material. The nutrient solution is supplied to each group of pans by conventional microfluidics channels which are incorporated into the liquid-impermeable support material. Therefore, in the known device, no conduction zone which would comprise microporous material is involved in the transport of the liquid from the application site to the target site, i.e., to the particular group of pans.
It is an object of the present invention to develop a congeneric device such that the flow rate is sped up without simultaneous pore enlargement and without increase in membrane thickness.